Abstract: Cervical cancer was once the leading cause of cancer death among women in the United States (U.S.). The implementation of comprehensive programs for screening, diagnosis, and treatment over the past 60 years has reduced cervical cancer incidence and mortality by more than 70% in the U.S. In contrast, cervical cancer remains the 1st or 2nd leading cause of cancer death among women in many low-and middle-income countries (LMICs). Cervical cancer prevention programs in low-resource settings are hampered by a lack of personnel with appropriate clinical expertise, lack of pathology services, and lack of associated infrastructure. Programs that involve multiple patient visits have a high rate of loss to follow-up. Screen-and-Treat approaches have been implemented in LMICs and include screening by HPV testing or visual inspection with acetic acid (VIA) followed by immediate treatment, reducing loss to follow-up; but these approaches lead to massive over-treatment due to the poor specificity of VIA and HPV testing. There is an urgent need for appropriate diagnostic tools to enable the implementation of a sensitive and specific Screen-Diagnose-Treat strategy that can be performed in a single patient visit in LMICs and in medically underserved areas of the U.S. We propose to develop and validate a low-cost Multimodal Mobile Colposcope (MMC) for global cervical Screen-Diagnose-Treat programs. This new device will combine the imaging capabilities of a smartphone- based colposcope developed by MobileODT with the microscopic imaging capabilities of a fiber-optic confocal imaging probe developed by Rice University. The MMC will image the entire cervix, automatically identify suspicious regions, and acquire co-registered high-resolution images of nuclear morphometry from suspicious areas. Multimodal image analysis algorithms will be developed in a study of 300 women referred for colposcopy at two sites in Brazil. The performance of the MMC with automated image analysis for detection of cervical precancer will be validated in a study of an additional 760 women referred for colposcopy in Brazil. We will determine the feasibility and usability of the MMC among low-resource setting providers by carrying out cancer prevention training courses using the MMC in Brazil. Our academic-industrial partnership includes expertise in bioengineering (Rice University), colposcopy and medical imaging (MobileODT), cervical cancer prevention and treatment (MD Anderson Cancer Center), and cervical cancer prevention and epidemiology (Albert Einstein College of Medicine), as well as the clinical expertise of our Brazilian clinical partners: Barretos Cancer Hospital and the Federal University of Health Sciences of Porto Alegre/Hospital Santa Casa. The innovative imaging technologies to be developed in this proposal will enable effective single-visit Screen-Diagnose-Treat programs to diagnose and treat women with cervical precancer while minimizing overtreatment.